绿原酸（CGA）是咖啡酸和奎宁酸相互作用产生的酚酸，被认为是许多清热解毒中药的主要活性成分，如金银花、鱼腥草、青蒿、栀子等CGA具有抗炎、抗氧化、抗癌、抗菌等特性。然而，CGA在肾脏纤维化中的作用和过程尚不清楚。为了探讨CGA减轻肾脏纤维化的治疗效果及其潜在机制，采用单侧输尿管梗阻（UUO）建立C57BL/6小鼠肾纤维化模型，并进行治疗使用 CGA（40、80 mg/kg/d），持续 10 天。收集血清和肾组织。通过网络药理学、分子对接和转录组分析来探索可能的机制。培养HK-2细胞，并用TGF-β1(10 ng/mL)和CGA(50、100 μM)处理，探讨TLR4/NF-κB信号通路在CGA抗肾纤维化治疗中的作用。 CGA 显着减轻 UUO 模型中的肾损伤、炎症、氧化应激和纤维化。 CGA还有效抑制体内和体外纤维化模型中炎症因子的表达和氧化应激过程。此外，转录组分析、分子对接和网络药理学结果表明，CGA对纤维化的治疗作用是通过调节TLR4/NF-κB信号通路来实现的。CGA可能通过以下方式调节炎症反应、氧化应激和纤维形成。调节 TLR4/NF-κB 信号通路对肾纤维化的影响。因此，CGA 是治疗肾纤维化的一种有吸引力的药物。本研究为肾纤维化治疗策略的进一步研究提供了基础。版权所有 © 2024。Elsevier B.V. 出版。

Chlorogenic acid (CGA), a phenolic acid produced by the interaction of Caffeic acid and Quinic acid, is considered to be the main active ingredient in many heat-clearing and detoxifying Chinese medicines, such as honeysuckle, Houttuynia, Artemisia annua, Gardenia, etc. CGA has anti-inflammatory, antioxidant, anticancer, antibacterial and other properties. However, the effect and process of CGA in kidney fibrosis remain unknown.To investigate the therapeutic effects of CGA on alleviating kidney fibrosis and the underlying mechanisms.C57BL/6 mouse kidney fibrosis model was established by unilateral uretera obstruction (UUO), followed by treatment with CGA (40, 80 mg/kg/d) for 10 days. The serum and kidney tissue were collected. Network pharmacology, molecular docking and transcriptomic analysis were conducted to explore the possible mechanisms. The HK-2 cells were cultured and treated with TGF-β1(10 ng/mL) and CGA (50, 100 μM), to examine the role of TLR4/NF-қB signaling pathway in the therapeutic effect of CGA on kidney fibrosis.CGA significantly alleviated kidney injury, inflammation, oxidative stress and fibrosis in UUO models. CGA also effectively inhibited the expression of inflammatory factors and the process of oxidative stress both in vivo and in vitro fibrosis models. Further, transcriptomic analysis, molecular docking, and network pharmacology results indicated that the therapeutic effect of CGA on fibrosis was through the regulation of TLR4/NF-қB signaling pathway.CGA might provide benefits for the regulation of inflammatory response, oxidative stress and fibrogenesis by modulating TLR4/NF-қB signaling pathway on kidney fibrosis. Hence, CGA is an attractive agent for treating kidney fibrosis. The present study provided a basis for further research on the therapeutic strategies of kidney fibrosis.Copyright © 2024. Published by Elsevier B.V.